Neurodegenerative disease is a kind of progressive disease associated with age including, for example, Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS). At present there are no effective methods for treating this kind of disease due to its unclear mechanism and complicated invasion cause.
As very important biological active molecules existed in the nerve system, neurotrophic factors (NTFs), such as nerve growth factor (NGF), can effectively promote regeneration and functional recovery of injured neuraxon. So, neurotrophic factors are considered as a potential drug for treating neurodegenerative diseases. However, effective clinical application of such neurotrophic molecules is restricted due to the insurmountable low bioavailability and specificity of large protein molecules.
In addition to the immunity system, FKBPs have been found to be present at high concentrations in the central nervous system. It has been found that the immunosuppressant FK506, as a potent inhibitor of FKBPs, can remarkably promote the neurite outgrowth and the nerve fiber differentiation, and show excellent blood-brain barrier penetrability and bioavailability[4]. However, when administered chronically, the immunosuppressant FK506 induces a number of potential side and toxic actions, including nephrotoxicity, such as impairment of glomerular filtration and irreversible interstitial fibrosis; and neurological deficits, such as involuntary tremors and non-specific cerebral angina.